Disulfide-mediated oligomer formation in Borrelia burgdorferi outer surface protein C, a critical virulence factor and potential Lyme disease vaccine candidate.

Abstract

Borrelia burgdorferi OspC is an outer membrane lipoprotein required for the establishment of infection in mammals. Due to its universal distribution among B. burgdorferi sensu lato strains and high antigenicity, it is being explored for the development of a next-generation Lyme disease vaccine. An understanding of the surface presentation of OspC will facilitate efforts to maximize its potential as a vaccine candidate. OspC forms homodimers at the cell surface, and it has been hypothesized that it may also form oligomeric arrays. Here, we employ site-directed mutagenesis to test the hypothesis that interdimeric disulfide bonds at cysteine 130 (C130) mediate oligomerization. B. burgdorferi B31 ospC was replaced with a C130A substitution mutant to yield strain B31::ospC(C130A). Recombinant protein was also generated. Disulfide-bond-dependent oligomer formation was demonstrated and determined to be dependent on C130. Oligomerization was not required for in vivo function, as B31::ospC(C130A) retained infectivity and disseminated normally. The total IgG response and the induced isotype pattern were similar between mice infected with untransformed B31 and those infected with the B31::ospC(C130A) strain. These data indicate that the immune response to OspC is not significantly altered by formation of OspC oligomers, a finding that has significant implications in Lyme disease vaccine design.

• Authors: Christopher G Earnhart, DeLacy V L Rhodes, Richard T Marconi
• Journal: Clinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 18 Issue 6 Pg. 901-6 (Jun 2011) ISSN: 1556-679X [Electronic] United States
• PMID: 21525304 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Bacterial
• Antigens, Bacterial
• Bacterial Outer Membrane Proteins
• Disulfides
• Immunoglobulin G
• Lyme Disease Vaccines
• OspC protein
• Virulence Factors
• Cysteine

Topics

• Amino Acid Substitution (genetics)
• Animals
• Antibodies, Bacterial (blood)
• Antigens, Bacterial (chemistry, genetics, immunology, metabolism)
• Bacterial Outer Membrane Proteins (chemistry, genetics, immunology, metabolism)
• Borrelia burgdorferi Group (genetics, immunology)
• Cysteine (genetics)
• Disulfides
• Immunoglobulin G (blood)
• Lyme Disease Vaccines (chemistry, genetics, immunology, metabolism)
• Mice
• Mice, Inbred C3H
• Mutagenesis, Site-Directed
• Protein Multimerization
• Virulence Factors (chemistry, genetics, immunology, metabolism)